Liposuction, also known as lipoplasty, liposculpture suction lipectomy or simply lipo, is a cosmetic surgery operation that removes fat from many different sites on the human body. Areas affected can range from the abdomen, thighs and buttocks, to the neck, backs of the arms and elsewhere.
Several factors limit the amount of fat that can be safely removed in one session. There are negative aspects to removing too much fat. Unusual lumpiness and/or dents in the skin can be seen in those patients “over-suctioned”. The more fat removed, the higher the surgical risk.
Injection lipolysis is a cosmetic procedure in which drug mixtures are injected into patients with the goal of destroying fat cells. This practice, using drugs generally based on phosphatidylcholine (PPC) and deoxycholate (DCA), evolved from the initial intravenous use of those drug formulations to treat blood disorders.
PPC is a class of phospholipids that incorporate choline as a head group. It is a major component of biological membranes and can be easily obtained from a variety of readily available sources, such as egg yolk or soybeans, from which it is mechanically or chemically extracted using hexane. PPC prevents fatty accumulation and is used to treat liver failure induced by fatty liver, myocardial ischemia, cerebrovascular diseases, and dementia. It has been also recently introduced for lipolysis for obesity treatment in the United States, Europe, and rest of the world.
DCA is one of the secondary bile salts, which are metabolic byproducts of intestinal bacteria. DCA has been used since its discovery in various fields of human medicine and is openly used in lipolysis injections, mixed with PPC. DCA has been used to improve the aqueous solubility of PPC and more recently, medications like amphotericin B, Taxol™, and diazepam. Highly purified PPC can be combined with the DCA, an anti-microbial, benzyl alcohol, and water to form a stable, mixed micelle preparation that can be rapidly sterilized and used for intravenous administration.
In 1966, investigators noted that the intravenous infusion of PPC-containing solutions could remove fat emboli. Later, a drug formulation called Lipostabil® containing 5% PPC and 4.75% DCA was approved in Germany and used in the treatment of fat embolism, dyslipidemia, and alcohol-induced liver cirrhosis.
Among detergents, bile salts are particularly potent solubilizers of lipid bilayer membranes. All biologic cell membranes are composed of the same bi-lipid layer structure, and are therefore subject to solubilization by detergents. Solubilization of cell membranes by a detergent involves distribution of the detergent between lipid bilayers, destabilization of the bilayer, disintegration, and subsequent formation of mixed micelles (composed of detergent and cell membrane lipid). Bile salts, and other detergents, decrease surface tension at the border of immiscible materials and allow the breakdown of large aggregates into smaller and smaller particles. In tissue, these agents dissolve cell membranes and cause cell lysis. An inflammatory response is generated by cell lysis, causing the body to remove the detergent solubilized material.
Recently, Kythera Biopharmaceuticals, a private company located in USA, is developing fat lipolysis injection using PPC free version of DCA. Based on PPC's role as an emulsifier in DCA and its use in the treatment of hyperlipidemia, PPC has been postulated as the active ingredient in lipolysis injection. Detergents, such as DCA, in these prior art compositions were added merely to disperse or solubilize the presumed active ingredient, PPC. However it was demonstrated that the DCA was actually the active agent for localized fat emulsification.
Because DCA is one of the strong detergents in the family of bile salts, treatment of PPC and DCA or DCA alone can evoke unwanted adverse events. Administration of DCA causes the destruction of surrounding tissues from injection sites. The use of DCA for a body fat removal is also associated with significant adverse events including pain, burning sensation, numbness, bruising, edema, swelling, pigmentation, and induration. Moreover, previous researchers suggest an increased risk of breast or colon cancer after DCA exposure.
While meeting with some success, prior techniques and compositions have met with certain limitations. Therefore it would be desirable to have a method of reducing localized fat accumulations that does not require surgery or prolonged recovery time and has fewer adverse side effects than currently available methods. The present invention fulfills this need.